POS1037 EFFECT OF GUSELKUMAB, A SELECTIVE IL-23p19 INHIBITOR, ON AXIAL-RELATED ENDPOINTS IN PATIENTS WITH ACTIVE PsA: RESULTS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY THROUGH 2 YEARS
Authors: P. J. Mease, P. Helliwell, D. D. Gladman, D. Poddubnyy, X. Baraliakos, S. D. Chakravarty, A. Kollmeier, X. L. Xu, S. Sheng, S. Xu, M. Shawi, D. Van der Heijde, A. Deodhar
Journal: Annals of the Rheumatic Diseases (2022)

Background Guselkumab (GUS), a selective IL-23p19 inhibitor, showed greater mean improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores vs placebo (PBO) at Week (W) 24 in patients (pts) with active PsA and investigator-confirmed sacroiliitis in pooled post hoc analyses of data from phase 3 DISCOVER (D)-1&amp;2 trials. Improvements in symptoms of axial involvement were maintained through 1 year. 1 Objectives To assess maintenance of GUS effect on symptoms of axial involvement in biologic-naïve PsA pts with investigator-confirmed sacroiliitis through 2 years of D-2. Methods In D-2, 739 bio-naïve pts with active PsA (≥5 swollen + ≥5 tender joints, CRP ≥0.6 mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100 mg every 4W (Q4W; n=245), GUS 100 mg at W0, W4, then Q8W (n=248), or PBO (n=246) with PBO→GUS 100 mg Q4W at W24. Pts with investigator-identified axial symptoms and sacroiliitis (prior X-ray or MRI, or pelvic X-ray at screening) were evaluated. Efficacy was assessed by changes in BASDAI, modified BASDAI (mBASDAI, excluding Q3 [peripheral joint pain]), and BASDAI Q2 (Spinal Pain) scores, and proportions of pts achieving BASDAI 50, Spinal Pain score ≤2, and AS Disease Activity Score (ASDAS) responses through W100. Through W24, pts who met treatment failure criteria or had missing data were considered nonresponders. After W24, missing data were imputed as nonresponse for binary endpoints or no change from baseline for continuous endpoints (nonresponder imputation [NRI]). Axial-related outcomes were also summarized by HLA-B27 status (+/-). Results 246 pts had investigator-confirmed sacroiliitis. Baseline characteristics were similar across treatment groups (62% male; mean age 44.4 years; mean BASDAI scores 6.5-6.6). At W24, LS mean/mean changes in BASDAI (-2.4/-2.6) and ASDAS (-1.3/-1.5) scores were greater in GUS- vs PBO-treated pts. Improvements were maintained through W100 in GUS-treated pts: BASDAI, -3.1; Spinal Pain, -3.1; mBASDAI, -3.1; ASDAS, -1.7. Response patterns were similar for BASDAI 50 response rates in GUS-treated pts (W24 38-40%; W100 49-54%). At W24, GUS-treated pts had higher response rates for achievement of ASDAS inactive disease, major improvement, and clinically important improvement vs PBO; response rates (NRI) were maintained, or in some cases further increased, at 2 years. Results were consistent for achievement of ASDAS LDA and Spinal Pain score ≤2 (data not shown). GUS-related improvements in axial symptoms through W100 were generally consistent in HLA-B27+/- pts (data not shown). Conclusion In bio-naïve pts with active PsA and investigator-confirmed sacroiliitis, GUS provided durable improvements in axial symptoms through W100, with substantial proportions of pts achieving and maintaining clinically meaningful improvements. References [1]Mease PJ et al. Lancet Rheumatol 2021;3:e715-723 Table 1. Axial symptom assessments through W100 in PsA pts with investigator-confirmed sacroiliitis in DISCOVER-2 (NRI ) GUS Q4W N=82 GUS Q8W N=68 PBO → GUS Q4W N=96 Change in BASDAI score W24 , LS mean (95% CI) -2.5 (-2.9, -2.0) -2.4 (-3.0, -1.8) -1.2 (-1.7, -0.7) Mean (SD) -2.5 (2.0) -2.6 (2.4) -1.4 (2.4) W52 , mean (SD) -2.9 (2.3) -2.7 (2.5) -2.9 (2.6) W100 , mean (SD) -3.0 (2.3) -3.1 (2.6) -3.3 (2.6) Change in mBASDAI (excludes Q3) score W24 , LS mean (95% CI) -2.4 (-2.9, -1.9) -2.4 (-2.9, -1.8) -1.2 (-1.7, -0.7) Mean (SD) -2.5 (2.1) -2.6 (2.5) -1.3 (2.3) W52 , mean (SD) -2.7 (2.6) -2.6 (2.5) -2.9 (2.4) W100 , mean (SD) -3.3 (2.6) -3.1 (2.6) -3.0 (2.4) Change in Spinal Pain (BASDAI Q2) score W24 , LS mean (95% CI) -2.2 (-2.7, -1.7) -2.3 (-2.9, -1.7) -0.9 (-1.5, -0.4) Mean (SD) -2.3 (2.6) -2.5 (2.8) -1.1 (2.5) W52 , mean (SD) -2.6 (2.7) -2.5 (2.7) -2.5 (2.7) W100 , mean (SD) -2.8 (2.7) -3.1 (2.8) -3.0 (2.8) Change in ASDAS score W24 , LS mean (95% CI) -1.3 (-1.6, -1.1) -1.3 (-1.6, -1.1) -0.6 (-0.8, -0.4) Mean (SD) -1.4 (1.0) -1.5 (1.2) -0.7 (1.1) W52 , mean (SD) -1.5 (1.1) -1.5 (1.3) -1.5 (1.3) W100 , mean (SD) -1.6 (1.2) -1.7 (1.2) -1.6 (1.2) Disclosure of Interests Philip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Philip Helliwell Speakers bureau: AbbVie, Janssen, and Novartis, Consultant of: Eli Lilly, Janssen, and Pfizer, Dafna D Gladman Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Abbvie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Denis Poddubnyy Consultant of: AbbVie, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, MDS, Novartis, and Pfizer, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Soumya D Chakravarty Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Shihong Sheng Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Stephen Xu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Global Services, LLC, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma, Employee of: Imaging Rheumatology BV, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith &amp; Kline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith &amp; Kline, Novartis, Pfizer, and UCB